Where Does Continuous Bioprocessing Feature In CMOs' Plans?
By Dr Nick Hutchinson, Contributor
It was recently estimated that approximately one third of biopharmaceutical manufacturing capacity is held by contract manufacturing organizations (CMOs) (Hernandez, 2015). Outsourcing the manufacture of biologics allows drug developers to focus on key activities such as the research and development of new medicines while leaving production to third parties with specialist skills and existing biomanufacturing facilities. CMOs must continuously enhance their core competency in bioproduction in order to maintain competitiveness, both against other CMOs and any internal manufacturing capacity that their customers might have and use rather than outsource. With this in mind, a prudent CMO might be expected to make R&D investments in innovative bioprocess technologies that will attract customers by reducing time to market, enhancing quality, or increasing process productivity.
In a recent BioPharm International survey of CMOs asking which technologies they believed would improve biomanufacturing performance, respondents cited the use of disposable technologies, better process development, better process control, and improved downstream operations (Langer, 2015). Conspicuous because of its absence from this list was continuous biomanufacturing methods, which are currently receiving considerable industry interest as a means of improving the efficiency of biopharmaceutical production (Warikoo et al., 2012). It seems that the most vociferous advocates of continuous production technologies come from biopharma companies themselves, and not from their outsourcing partners. A quick review of leading CMOs’ websites shows that their promotion of continuous biomanufacturing capacity is muted. It is hard to identify a CMO that, having identified a gap in the market, is attempting to emphasize its position as an expert in this field. What might the causes be that would lead to a discrepancy between apparent demand for fully continuous capacity and the supply from biomanufacturing CMOs?
In his article, Langer rightly highlights the important role that CMOs have played in the adoption of single-use technologies. The introduction of disposable technology was arguably one of the last major innovations in the biomanufacturing sector. Perhaps unlike continuous processing, however, the technology provides clear benefit to CMOs themselves. In a multi-product facility into which processes must be readily transferred, single-use technologies reduce the risk of contaminations between batches of different products and enable tremendous flexibility to facilitate the fit of different processes to the facility. Further, they reduce the cost of the assets that CMOs hold and finance. The higher costs of consumables can potentially be passed on to customers.
The introduction of continuous biomanufacturing processes may come with more costs and fewer benefits to CMOs. As Langer & Rader (2014) point out in an earlier article, the science behind continuous bioprocessing — to a greater extent than perfusion — still needs elucidating. Significant investments in R&D are likely to be required to develop and integrate upstream and downstream processing steps, which will eat into profits in the short term. The results of this technology development will take time. It could be that CMOs are currently in this phase of implementation and are deliberately keeping this work under the radar. If intellectual property rights can be obtained in this space the rewards could be significant.
It seems unlikely that existing production assets will be able to be reconfigured to adapt to increasing demand in continuous production methods. One of the key benefits of continuous biomanufacturing will be the more efficient utilization of smaller production equipment which risks leaving large-scale assets suitable for batch production either redundant or under-utilized. To implement fully continuous processing will, therefore, require raiding the capital expenditure budget for new processing technology. This will likely have to be more sophisticated than that currently used for batch processing because of the need to reliably control high-value product streams that are continuously in motion. In fact, not only will support equipment have to change, but CMOs may need to consider changing a plethora of operational practices including shift patterns, documentation, training, and approach to quality assurance.
The implementation of continuous bioprocessing into CMOs is unlikely to be a trivial task. CMOs have profited in the past from clients who were not prepared to invest in their own assets because they were not ready, or never intended, to make manufacturing a core competency of their own. CMOs also could rely on a pool of clients that had similar manufacturing needs and could therefore be accommodated into process platforms. If CMOs are seeking to replicate this model in an expanded production portfolio which includes continuous manufacturing capabilities, they will want to be as confident as possible that the industry has, or could soon, converge upon a continuous process configuration. This, ultimately, could be the current stumbling block. The level of uncertainty around the true level of demand for continuous capacity or the exact requirements of customers wanting these services may be too high at the moment to warrant the level of investment needed to implement this type of technology.
The competitive advantage to be gained from being the first CMO to attempt to adopt a market leading position in continuous bioprocessing may not be considered a big enough prize to warrant taking abnormal risks. Rather than expecting established players to lead in this area, it seems more likely that continuous bioprocessing capacity available for outsourcing will be pioneered by smaller companies with more share of the market to gain and less reputation to lose. Biding time and correctly deciphering market signals without being biased by industry hyperbole is, of course, the shrewd move, but only so long as companies do not wind up being too late to the party. Continuous bioprocessing could be a disruptive technology for the CMO industry.
R. Hernandez, “Fluctuating Capacity and Demand Conditions in Biomanufacturing,” Biopharm International eBooks 28 (14) 2015.
E. Langer, “CMOs Continue to Improve Overall Biomanufacturing Performance,” BioPharm International 28 (11) 2015.
E. Langer & R Rader, “Continuous Bioprocessing and Perfusion: Wider Adoption Coming as Bioprocessing Matures,” Bioprocessing Journal. Spring 2014.
V. Warikoo et al., “Integrated continuous production of recombinant therapeutic proteins,” Biotechnology and Bioengineering 109 (12) 2012.
Dr Nick Hutchinson holds a Masters degree and a Doctorate in Biochemical Engineering from University College London in the UK. He has worked in bioprocess research and process transfer roles within the CMO sector for a number of years. He has since worked in various marketing roles for a supplier of single-use technology and is now an observer of the biomanufacturing industry who enjoys communicating what he sees with the aim of stimulating debate, ideas and even a little controversy if it helps move the industry forward.